AVAJAK: Apixaban/rivaroxaban Versus Aspirin for primary prevention of thrombo-embolic complications in JAK2V617F-positive myelo-proliferative neoplasms

Phase 1

• Conditions: Myelo-proliferative neoplasms including essential thrombocythemia, Polycythemia Vera, Prefibrotic myelofibrosis; MedDRA version: 20.0Level: PTClassification code 10077465Term: Myeloproliferative neoplasmSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10015494Term: Essential thrombocythemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10036061Term: Polycythemia veraSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10028537Term: MyelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-004652-15-FR
• Lead Sponsor: CHRU de Brest

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-04-16
• Last Update Posted: 5 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1340

Inclusion Criteria

- Patients with diagnosis of PV or ET or PreMF according to WHO or BSCH criteria (bone marrow biopsy not compulsory).
- Patients with JAK2V617F mutation (threshold allele burden > 1%).
- Patients considered as high-risk” patients:
1°) based on age (> 60-year-old)
2°) based on thrombotic history (compatible with antithrombotic randomization) but aged = 18-year-old.
- Length of time from MPN diagnostic to inclusion will not exceed 12 months.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Contra-indication to aspirin or DOAC due to allergic situation or recent history of major bleeding
- Formal indication of treatment with LDA or DOAC (thus precluding randomization)
- Inability to give informed consent
- Patients under curatorship/guardianship
- Concomitant use of a strong inhibitor or inducer of CYP3A4 (like Ruxolitinib).
- Chronic liver disease or chronic hepatitis
- Renal insufficiency with creatinine <25 ml/mn on Cockcroft and Gault Formula
- Patient considered at high-risk of bleeding
- Active or expected pregnancy
- No effective contraception in women of childbearing age
- PS>2 or life expectancy <12 months

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate that low-dose DOAC is more effective than LDA in the primary prevention of arterial or venous thrombosis in JAK2V617F-positive high-risk MPN patients. ;Secondary Objective: Secondary objectives greater than 1000 characters (refer to the protocol);Primary end point(s): Occurrence of arterial or venous thromboembolic events at 24 months.;Timepoint(s) of evaluation of this end point: 3, 6, 12, 18 and 24 month

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Occurrence of major and clinically relevant non-major bleedings as defined by ISTH at 24 months.<br>- Occurrence of arterial thromboembolic events at 24 months.<br>- Occurrence of venous thromboembolic events at 24 months.<br>- Occurrence of serious adverse events others than thrombosis and bleedings at 24 months.<br>- Occurrence of atrial fibrillation episodes at 24 months.<br>- Overall survival and event free survival (events defined above) at 24 months.<br>- Occurrence of adjudicated mortality (non cardiovascular and cardiovascular) at 24 months<br>- Therapeutic adherence will be studied (Girerd auto-questionnaire) during the study treatment period of 24 months.<br>- Quality of life will be studied (EQ-5D-5L and MPN-SAF auto-questionnaire) during the study treatment period of 24 months.<br>- Evaluation of costs and incremental cost utility ratio (cost per QALY) of low-dose DOAC compared to LDA.<br>;Timepoint(s) of evaluation of this end point: 3, 6, 12, 18 and 24 month